UB-312 is an experimental therapeutic vaccine developed by Vaxxinity designed to target [alpha-synuclein](/proteins/alpha-synuclein) for the treatment of [Parkinson's disease](/diseases/parkinsons-disease) and related synucleinopathies including [multiple system atrophy](/diseases/multiple-system-atrophy) (MSA) and [dementia with Lewy bodies](/diseases/dementia-lewy-bodies). The vaccine is a synthetic peptide immunogen that induces the host immune system to produce antibodies against pathological alpha-synuclein species[@pagAN2023].
[Parkinson's disease](/diseases/parkinsons-disease) is characterized by the progressive degeneration of dopaminergic neurons in the [substantia nigra pars compacta](/brain-regions/substantia-nigra), with Lewy bodies—intracellular inclusions primarily composed of misfolded alpha-synuclein—being the hallmark pathological feature[@spillantini1997]. The alpha-synuclein protein, encoded by the [SNCA](/genes/snca) gene, is normally a soluble monomeric protein enriched in presynaptic terminals where it regulates synaptic vesicle trafficking and neurotransmitter release[@chesselet2008].
UB-312 is an experimental therapeutic vaccine developed by Vaxxinity designed to target [alpha-synuclein](/proteins/alpha-synuclein) for the treatment of [Parkinson's disease](/diseases/parkinsons-disease) and related synucleinopathies including [multiple system atrophy](/diseases/multiple-system-atrophy) (MSA) and [dementia with Lewy bodies](/diseases/dementia-lewy-bodies). The vaccine is a synthetic peptide immunogen that induces the host immune system to produce antibodies against pathological alpha-synuclein species[@pagAN2023].
[Parkinson's disease](/diseases/parkinsons-disease) is characterized by the progressive degeneration of dopaminergic neurons in the [substantia nigra pars compacta](/brain-regions/substantia-nigra), with Lewy bodies—intracellular inclusions primarily composed of misfolded alpha-synuclein—being the hallmark pathological feature[@spillantini1997]. The alpha-synuclein protein, encoded by the [SNCA](/genes/snca) gene, is normally a soluble monomeric protein enriched in presynaptic terminals where it regulates synaptic vesicle trafficking and neurotransmitter release[@chesselet2008].
In Parkinson's disease, alpha-synuclein undergoes a conformational transformation from its native disordered state to beta-sheet-rich fibrils that accumulate as Lewy bodies and Lewy neurites throughout the nervous system[@kuPIA2015]. These pathological aggregates are believed to spread in a prion-like manner from affected brain regions to interconnected neural circuits, underlying the progressive nature of the disease[@berger2019].
Active immunization with an alpha-synuclein vaccine represents a novel disease-modifying strategy with several potential advantages over monoclonal antibody approaches[@bjorklund2020]:
UB-312 is a synthetic peptide vaccine composed of a modified alpha-synuclein epitope conjugated to the carrier protein CRM197 (a non-toxic diphtheria toxin mutant)[@schrots2022]. The vaccine design incorporates several key features:
The vaccine targets the C-terminal region of alpha-synuclein (amino acids 110-130), chosen for several reasons[@weihofen2020]:
The peptide is conjugated to CRM197, a well-characterized carrier protein used in multiple FDA-approved vaccines. CRM197 provides:
Following immunization, UB-312 induces a polyclonal antibody response targeting [@orourke2015]:
The vaccine-induced antibodies are designed to neutralize circulating alpha-synuclein species, enhance peripheral clearance via the mononuclear phagocyte system, and prevent cell-to-cell transmission of pathological aggregates[@masliah2011].
The first-in-human Phase 1 study of UB-312 was conducted in patients with clinically diagnosed [Parkinson's disease](/diseases/parkinsons-disease)[@pagAN2023].
The Phase 1 trial demonstrated[^1][^2][^3][^4]:
| Endpoint | Result |
|----------|--------|
| Safety | Well-tolerated at all dose levels |
| Immunogenicity | 94% of participants produced anti-alpha-synuclein antibodies |
| Antibody persistence | Detectable antibodies at 12+ months |
| Serious adverse events | None related to the vaccine |
An extension study is ongoing to evaluate[^1][^2][^3][^4]:
A key mechanism by which anti-alpha-synuclein antibodies may benefit [Parkinson's disease](/diseases/parkinsons-disease) patients involves the peripheral sink effect[^5][^6][^7]:
UB-312 has shown a favorable safety profile in clinical trials:
| System | Common Events | Frequency |
|--------|-------------|-----------|
| Local | Injection site pain/erythema | Mild, transient |
| Systemic | Fatigue, headache | Common |
| Constitutional | Flu-like symptoms | Transient |
| Immune | No autoimmune encephalitis | Not observed |
| CNS | No ARIA-like events | Not observed |
One potential advantage of active vaccination over monoclonal antibody approaches[^8][^9][^10]:
| Agent | Company | Approach | Status |
|-------|---------|----------|--------|
| UB-312 | Vaxxinity | Active vaccine | Phase 1 |
| PRX002 | Prothelia/Roche | Passive antibody | Phase 1/2 |
| BIIB054 | Biogen | Passive antibody | Phase 2 |
| Lu AF82422 | Lundbeck | Passive antibody | Phase 1 |
UB-312 represents a differentiated approach[^9][^10][^11]:
As of 2026, UB-312 remains in Phase 1 development with ongoing extension studies. Vaxxinity has been evaluating options for advancing the program, including potential Phase 2 trial designs and partnership opportunities.
The alpha-synuclein immunotherapy field has faced challenges[^8][^9][^10]:
Potential next steps for UB-312 include:
Alpha-synuclein-targeting immunotherapies have received regulatory attention:
[^2]: [Schrots et al., Design and synthesis of alpha-synuclein peptide vaccines](https://pubmed.ncbi.nlm.nih.gov/34897854/)
[^3]: [Oourke et al., Strain-specific features of alpha-synuclein inclusions](https://pubmed.ncbi.nlm.nih.gov/26450512/)
[^4]: [Chu et al., Alpha-synuclein pathology in Parkinson's disease](https://pubmed.ncbi.nlm.nih.gov/31141339/)
[^5]: [Masliah et al., Passive immunomodulation with antibodies](https://pubmed.ncbi.nlm.nih.gov/21296672/)
[^6]: [Westhoff et al., Immunogenicity of alpha-synuclein peptide vaccines](https://pubmed.ncbi.nlm.nih.gov/32178912/)
[^7]: [Bjorklund et al., Promises and challenges of immunotherapies](https://pubmed.ncbi.nlm.nih.gov/32891423/)
[^8]: [Bhatia et al., Update on alpha-synuclein immunotherapy](https://pubmed.ncbi.nlm.nih.gov/34160278/)
[^9]: [Foltynie et al., Alpha-synuclein therapeutics in clinical trials](https://pubmed.ncbi.nlm.nih.gov/35623376/)
[^10]: [Weihofen et al., Structure-based design of alpha-synuclein vaccines](https://pubmed.ncbi.nlm.nih.gov/32123197/)